Imidazo[1,2- a ]Pyridine Derivatives as Novel Dual-Target Inhibitors of ABCB1 and ABCG2 for Reversing Multidrug Resistance.

ABCB1 and ABCG2 are the important ATP-binding cassette (ABC) transporters associated with multidrug resistance (MDR). Herein, we designed a series of imidazo[1,2-]pyridine derivatives as dual-target inhibitors of ABCB1 and ABCG2 through the scaffold hopping strategy. Compound displayed potential efflux function inhibitory toward both ABCB1 and ABCG2 (reversal fold: ABCB1 = 8.35 and ABCG2 = 2.71) without obvious cytotoxicity. also enhanced the potency of antiproliferative drugs in vitro. Mechanistic studies demonstrated that slightly suppressed ATPase activity but did not affect the protein expression of ABCB1 or ABCG2. Notably, exhibited negligible CYP3A4 inhibition and enhanced the antiproliferative activity of adriamycin in vivo by restoring the sensitivity of resistant cells. Thus, may be effective clinically in combination with common chemotherapy agents. In summary, is a potential dual-target inhibitor that reverses MDR by blocking the efflux function of ABCB1 and ABCG2.